The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Notch3  -  notch 3

Rattus norvegicus

Synonyms: Neurogenic locus notch homolog protein 3, Notch 3
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Notch3

  • Intriguingly, enforced Notch1 signaling up-regulates expression of Notch3, which has also been implicated in the pathogenesis of T-ALL [1].
  • Mutations in the Notch3 receptor result in the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephelopathy (CADASIL) syndrome, a heritable arteriopathy predisposing to early onset stroke [2].

High impact information on Notch3

  • Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs) [3].
  • We initially established that both transient and constitutive Notch3 signaling promoted VSMC survival in response to the proapoptotic Fas ligand (FasL) [2].
  • Taken together, these findings provide initial evidence that Notch3 signaling may be a critical determinant of VSMC survival and vascular structure by modulating the expression of downstream mediators of apoptosis via signaling cross-talk with the ERK/MAPK pathway [2].
  • Notch 2 is related to both proliferation and maturation of spermatogenic cells, whereas Notch 3 seems to be related to Leydig cell functions [4].
  • Notch-3 expression was limited to Leydig cells [4].

Chemical compound and disease context of Notch3

  • To examine the functional consequences of CADASIL mutations, we engineered 4 CADASIL-like mutations into rat Notch3 and have shown that the presence of an unpaired cysteine does not impair cell-surface expression or ligand binding [5].

Biological context of Notch3


Anatomical context of Notch3

  • Both Notch1 and Notch3 mRNAs are expressed along the inner aspect of the dentate gyrus, a site of adult neurogenesis [6].
  • Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate [3].
  • Based upon clinical evidence that CADASIL arteriopathy results in degeneration and loss of vascular smooth muscle cells (VSMC) from the arterial wall, we postulated that Notch3 signaling is a critical determinant of VSMC survival [2].
  • This study documents that the Notch-3 receptor, the ligand Jagged-1, and the downstream transcription factor, HESR-1, are expressed in the normal adult rat carotid artery, and that this expression is modulated after vascular injury [7].

Analytical, diagnostic and therapeutic context of Notch3

  • In injured teeth, Notch2 was expressed in mesenchymal cells of the pulp both close to the site of injury (i.e., in the dental crown) and at a distance from it (i.e., in the dental roots), Notch3 expression was mainly associated with vascular structures, while Notch1 expression was restricted to few pulpal cells close to the lesion [8].


  1. Unexpected features of acute T lymphoblastic lymphomas in Notch1IC transgenic rats. van den Brandt, J., Kwon, S.H., McPherson, K.G., Petrovic, S., Zettl, A., Müller-Hermelink, H.K., Reichardt, H.M. Eur. J. Immunol. (2006) [Pubmed]
  2. Notch3 signaling in vascular smooth muscle cells induces c-FLIP expression via ERK/MAPK activation. Resistance to Fas ligand-induced apoptosis. Wang, W., Prince, C.Z., Mou, Y., Pollman, M.J. J. Biol. Chem. (2002) [Pubmed]
  3. Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Tanigaki, K., Nogaki, F., Takahashi, J., Tashiro, K., Kurooka, H., Honjo, T. Neuron (2001) [Pubmed]
  4. Effect of experimental varicocele on the expressions of Notch 1, 2, and 3 in rat testes: an immunohistochemical study. Sahin, Z., Bayram, Z., Celik-Ozenci, C., Akkoyunlu, G., Seval, Y., Erdogru, T., Ustunel, I., Baykara, M., Demir, R. Fertil. Steril. (2005) [Pubmed]
  5. CADASIL Notch3 mutant proteins localize to the cell surface and bind ligand. Haritunians, T., Boulter, J., Hicks, C., Buhrman, J., DiSibio, G., Shawber, C., Weinmaster, G., Nofziger, D., Schanen, C. Circ. Res. (2002) [Pubmed]
  6. Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. Irvin, D.K., Zurcher, S.D., Nguyen, T., Weinmaster, G., Kornblum, H.I. J. Comp. Neurol. (2001) [Pubmed]
  7. Determinants of Notch-3 receptor expression and signaling in vascular smooth muscle cells: implications in cell-cycle regulation. Campos, A.H., Wang, W., Pollman, M.J., Gibbons, G.H. Circ. Res. (2002) [Pubmed]
  8. Reactivation of Delta-Notch signaling after injury: complementary expression patterns of ligand and receptor in dental pulp. Mitsiadis, T.A., Fried, K., Goridis, C. Exp. Cell Res. (1999) [Pubmed]
WikiGenes - Universities